Mohamed Abdel-Mohsen, de la Northwestern University de Chicago, completará la sesión inaugural del XVI Congreso Nacional de GeSIDA con una ponencia sobre estrategias dirigidas al huésped basadas en biomarcadores, sobre la que nos avanza algunas claves en esta entrevista.
Your research focuses on host-targeted rather than virus-targeted strategies. What advantages does this approach offer compared to classic antiviral therapies?
We believe the likelihood of viral rebound after stopping antiretroviral therapy (ART) reflects two forces: (1) virological; i.e., the size and inducibility of HIV reservoirs in blood and tissues; and (2) host pressures on these reservoirs. Host-targeted biomarkers and interventions can therefore be an important complement to virus-directed approaches, and together they may shape rebound kinetics and help maintain viral remission in the absence of ART.
Which biomarkers are emerging as most promising for guiding personalized therapies in people with HIV?
Markers of tissue stress, inflammaging, and specific features of immune dysfunction correlate with faster rebound and lack of control. Some of these may indirectly reflect a higher burden of total or inducible reservoir, especially in tissues, while others point to pathways that are tractable and could be leveraged to enhance immune control of inducible HIV reservoirs during and after treatment interruption.
To what extent do inflammatory and immunosenescence processes influence the success of cure strategies?
To a great extent. These inflammatory and immunosenescence processes shape the immunologic pressures on HIV reservoirs during and after treatment interruption and, depending on context, can influence the dynamics of rebound and the prospects for cure.
What role could biomarkers play in identifying patients who are candidates for interventions aimed at viral remission or eradication?
Two roles: (1) Defining individuals more likely to achieve a controller phenotype after an intervention, so they are appropriate for analytic treatment interruption, reducing the risks of stopping ART in those with a low likelihood of control; and (2) even more importantly, pointing to specific host pathways that may actively contribute to control and can be targeted to improve current cure strategies or inspire new ones.
From a translational perspective, what barriers remain to overcome before host-targeted strategies reach clinical practice?
The number of samples available to identify consistent, reproducible signatures of rebound is limited because most people with HIV do not undergo treatment interruption outside trials. Trial criteria and endpoints also vary, making it difficult to combine datasets across studies. Together, these issues hinder classic biomarker discovery efforts that yield high-confidence, generalizable markers, or at least clarify which demographic and clinical factors modify biomarker–rebound relationships in different populations.
What research areas do you consider priorities for the coming years in this field?
I think the connection between chronic inflammation/immunosenescence and HIV cure should be investigated more deeply, both mechanistically and in prospective studies. Priorities include harmonized analytic treatment interruption cohorts for biomarker validation, tissue-level studies (gut, lymph nodes, CNS) to map inducible reservoirs, and testing host-pathway–targeted interventions alongside existing cure strategies.